Direct Implantation of Patient Brain Tumor Cells into Matching Locations in Mouse Brains for Patient-Derived Orthotopic Xenograft Model Development

Lin Qi, Patricia Baxter, Mari Kogiso, Huiyuan Zhang, Frank K. Braun, Holly Lindsay, Sibo Zhao, Sophie Xiao, Aalaa Sanad Abdallah, Milagros Suarez, Zilu Huang, Wan Yee Teo, Litian Yu, Xiumei Zhao, Zhigang Liu, Yulun Huang, Jack M. Su, Tsz Kwong Man, Ching C. Lau, Laszlo PerlakyYuchen Du*, Xiao Nan Li*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: Despite multimodality therapies, the prognosis of patients with malignant brain tumors remains extremely poor. One of the major obstacles that hinders development of effective therapies is the limited availability of clinically relevant and biologically accurate (CRBA) mouse models. Methods: We have developed a freehand surgical technique that allows for rapid and safe injection of fresh human brain tumor specimens directly into the matching locations (cerebrum, cerebellum, or brainstem) in the brains of SCID mice. Results: Using this technique, we successfully developed 188 PDOX models from 408 brain tumor patient samples (both high-and low-grade) with a success rate of 72.3% in high-grade glioma, 64.2% in medulloblastoma, 50% in ATRT, 33.8% in ependymoma, and 11.6% in low-grade gliomas. Detailed characterization confirmed their replication of the histopathological and genetic abnormalities of the original patient tumors. Conclusions: The protocol is easy to follow, without a sterotactic frame, in order to generate large cohorts of tumor-bearing mice to meet the needs of biological studies and preclinical drug testing.

Original languageEnglish (US)
Article number1716
JournalCancers
Volume16
Issue number9
DOIs
StatePublished - May 2024

Funding

This work was funded by NIH RO1 CA185402 (Li XN), NIH/NCI Pediatric Preclinical Testing Consortium UO1 (1U01CA199288) (Li XN), NIH/NCI Patient-Derived Models of Cancer (PDMC) (UO1 1-U01-CA217613-01A1) (Li XN), NIH/NCI Pediatric Preclinical In Vivo Testing Program (PIVOT) (2UO1 CA199288-06) (Li XN), the Cancer Prevention & Research Institute of Texas (CPRIT) RP150032 and RP-170169 (Li XN), Cure Starts Now Foundation (Li XN), Golfers against Cancer (Li XN), CDMRP DOD PRCRP CA100735 (Li XN), the Childhood Brain Tumor Foundation (Li XN), National Brain Tumor Foundation (LI XN), and St. Baldrick\u2019s Foundation (Grant 2532341503, Su JM).

Keywords

  • brain tumor
  • cancer
  • orthotopic xenograft model

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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